纤维软骨性结构不良23例临床病理和分子特征分析

Clinicopathological and molecular features of fibrocartilaginous dysplasia: analysis of 23 cases

目的探讨纤维软骨性结构不良(fibrocartilaginous dysplasia,FCD)的临床病理和分子特征。方法回顾性分析23例FCD的临床病理和影像学特征,运用免疫组化和Sanger测序法分析FCD的免疫表型和分子特征。结果23例FCD中男性14例,女性9例,发病年龄9~55岁,中位年龄19岁。3例为多骨性病变,其余为单骨性病变。病变主要发生于股骨(18/23),尤其好发于股骨颈;余肱骨2例,胫骨、髂骨和指骨各1例。影像学大多数表现为界限清楚的膨胀性磨玻璃样背景中见点状、环状或絮状钙化。镜检:病变内可见增生的纤维母细胞和不成熟编织骨,以及多少不等的高分化透明软骨成分及软骨化骨。免疫表型:纤维骨性成分均表达SATB2,Ki-67增殖指数低,不表达CK、CK5/6、p63等上皮标志物。6例分子检测提示GNAS基因第8外显子突变,分别为CGT>TGT导致的p.R201C位点突变(2例)和CGT>CAT导致的p.R201H位点突变(4例),不同形态区域突变位点一致;IDH1/IDH2均为野生型。结论FCD是少见纤维结构不良特殊形态学亚型。纤维骨性成分和软骨成分同源,软骨成分是纤维结构不良发生、发展过程中的组成部分。纤维结构不良中出现软骨,再结合影像学改变和分子检测可辅助FCD的诊断。

Purpose To explore the clinicopathologic and molecular features of fibrocartilaginous dysplasia.Methods The clinicopathological and imaging features of 23 cases of fibrocartilaginous dysplasia were retrospectively analyzed.Immunophenotypes and molecular features were detected by immunohistochemistry and sanger sequencing respectively.Results Twenty-three cases of fibrocartilaginous dysplasia were identified,including 14 males and 9 females at a mean age of 19 years(range,9-55 years).Three cases were polyostotic and the rest were monostotic.The femur was the most common sites involved(18/23),especially in femoral neck.Imaging showed well-defined radiolucent lesions with varying proportions stippled calcifications.Bland fibroblastic cells and irregular curvilinear trabeculae of woven bone were observed morphologically.Benign hyaline cartilage islands and variable enchondral ossification merging with the surrounding fibro-osseous lesion were observed.Positive immunoreaction with SATB2 was demonstrated in the fibro-osseous tissues.Ki-67 index was low.GNAS point mutation was detected in all the 6 cases,2 cases in p.R201C and 4 cases in p.R201H,which showed no difference between fibro-osseous and carlaginous components in the same case.IDH1/IDH2 was proved to be wild type.Conclusion Fibrocartilaginous dysplasia is a rare morphological variant of fibrous dysplasia.These results suggest that the cartilaginous components are an integral part of fibrous dysplasia according to the immunohistochemical and molecular findings.Awareness of the cartilage component in fibrous dysplasia is helpful in the diagnosis and differential diagnosis in combination with imaging and molecular testing.